DCTN1 encodes dynactin subunit 1 (p150Glued), a critical component of the dynactin motor protein complex that activates dynein for processive microtubule-based transport 1. DCTN1 recruits dynein to cargos and microtubules, enhancing dynein processivity while also functioning as a brake to regulate motor speed 2. Beyond transport, DCTN1 stabilizes microtubules by promoting polymerization and inhibiting catastrophe through simultaneous binding to microtubules and tubulin 3. DCTN1 also regulates centriole cohesion, subdistal appendage organization, and primary cilia formation 45. Clinically, DCTN1 mutations cause Perry syndrome, an autosomal dominant neurodegenerative disorder featuring parkinsonism, psychiatric symptoms, weight loss, central hypoventilation, and distinctive TDP-43 pathology 1. DCTN1 mutations are also associated with distal hereditary motor neuropathy with vocal cord palsy, amyotrophic lateral sclerosis, and atypical parkinsonism presentations 678. Recently, DCTN1 phosphorylation by PLK2 was shown to impair autophagosome-lysosome fusion, exacerbating α-synuclein pathology in Parkinson disease 9. Additionally, DCTN1-ALK fusion genes have been identified in rare ALK-positive histiocytosis cases with neurologic involvement 10.